京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13371号 / 論医博第2208号 / 新制||医||1047(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 妹尾 浩, 教授 浅野 雅秀 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Segmented analysis of subcortical structures within the nonhuman primate can potentially have a profound impact on studying the relationship between volumetric characteristics and alcohol dependencies. Image segmentations have been widely used in quantifying structural information. There are a variety of methods in which users can extract desired structures from a medical image; ranging from manual segmentations to fully-automated segmentations and 2-D to 3-D. The implications of this possibility can have tremendous applicability to medical research and diagnosis. The primary goal of my thesis is to investigate different implementation methodologies for segmenting subcortical structures such as the hippocampus and striatum and then apply that knowledge towards the development of an approach to segment these two structures from a group of alcohol-dependent Rhesus Macaque monkeys. Using the Level Set Deformable Model (LSDM) with a priori structural information, a series of T1-weighted MR images of Rhesus Macaque hippocampi and striatum were segmented in an effort to compare the structural hippocampal and striatal volumes between early and late stages of alcohol dependency. The results suggest that the volumes of both subcortical structures are affected negatively by alcoholism. Volume deficits of as much as 5% for the hippocampus and 8% for the caudate were found. / Master of Science

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Submitted by Tatiana Lima (tatianasl@ufba.br) on 2015-05-15T18:54:51Z No. of bitstreams: 1 Bittencourt, Silvia Conceição.pdf: 740824 bytes, checksum: ab8a5859ac30fe3b831aa809b25d1c3f (MD5) / Approved for entry into archive by Tatiana Lima (tatianasl@ufba.br) on 2015-05-15T18:59:24Z (GMT) No. of bitstreams: 1 Bittencourt, Silvia Conceição.pdf: 740824 bytes, checksum: ab8a5859ac30fe3b831aa809b25d1c3f (MD5) / Made available in DSpace on 2015-05-15T18:59:24Z (GMT). No. of bitstreams: 1 Bittencourt, Silvia Conceição.pdf: 740824 bytes, checksum: ab8a5859ac30fe3b831aa809b25d1c3f (MD5) / A Constituição Federal aprovada em 1988 pautada em valores vinculados aos direitos humanos, não conseguiu operacionalizá-los no desenvolvimento das suas políticas públicas, em especial na Política Pública de Saúde. Em vinte e cinco anos de existência do Sistema Único de Saúde (SUS) muitos foram os avanços, entretanto, estes não foram capazes de superar a predominância de um modelo de atenção e gestão à saúde hospitalocêntrico, caracterizado pelos seguintes aspectos: médico centrado, com práticas vinculadas ao excesso de tecnologia e especializações, as quais se vinculam a métodos denominados como “desumanos”. Nesse contexto, a gestão federal da Saúde, no ano de 2003, propõe a implantação da Política Nacional de Humanização (PNH), a qual reflete um conjunto de estratégias, diretrizes e dispositivos, dirigidas para superar essa realidade crítica no SUS. Assim, esse estudo pretende analisar as estratégias desenvolvidas pela gestão (Federal, Estadual e Local) para a implantação das diretrizes e dispositivos da PNH na emergência de uma unidade hospitalar pública no Estado da Bahia, no período de janeiro de 2012 a agosto de 2013. Trata-se de uma pesquisa qualitativa, tomando como base teórico-metodológica o conceito de Administração Política, a partir da análise de um estudo de caso de uma emergência hospitalar selecionada. O resultado ratificou a dificuldade da gestão e gerência da unidade em implantar as diretrizes dessa política, uma vez que seus pressupostos teóricometodológicos não coadunam com o projeto societário hegemônico do Estado (que reflete a concepção neoliberal que fundamenta a atual dinâmica do capitalismo internacional e nacional). Essa situação fragiliza a operacionalização das estratégias da Política analisada no cotidiano da prestação do serviço. Diante dessa análise, foi sugerida uma agenda propositiva para a melhoria da gestão e gerência da PNH, a fim de contribuir para o processo de transformação social defendido pelo projeto de Reforma Sanitária Brasileira (RSB), na busca, pois, de efetivar os princípios estruturantes do SUS já consagrados na CF de 1988. / The adoption of the Federal Constitution of 1988 , based on values related to human rights, failed to operationalize them in developing their public policies, especially in Public Health Policy In twenty -five years of existence of the Unified Health System (SUS) there have been many advances, however, they were not able to overcome the dominance of a model of care and management of hospital-centered health, characterized by the following aspects : centered medical practices related to the excess of technology and expertise , which are linked to methods referred to as "inhuman". In this context, the federal management of Health , in 2003, proposed the establishment of the National Humanization Policy (NHP), which reflects a set of strategies, guidelines and devices directed to overcome this critical reality of SUS . Thus, this study aims to examine the strategies developed by management (Federal , State and Local) for the implementation of the guidelines and provisions of PNH in the emergence of a public hospital in the state of Bahia, from 2012 to August 2013. This is a qualitative research, taking as theoretical and methodological basis the concept of Policy Administration, from the analysis of a case study of a hospital emergency selected. The result confirmed the difficulty of management and site management in implementing the guidelines of this policy, since its theoretical and methodological assumptions not consistent with the hegemonic social project of the State (which reflects the neoliberal conception that underlies the current dynamics of global capitalism and national). This undermines the operationalization of policy strategies analyzed in everyday provide service. Given this analysis, it was suggested that a proposed for improving management and management of NHP in order to contribute to the process of social change advocated by the Health Reform Project (RSB), seeking thus to effect the structural principles SUS already enshrined in the 1988 Constitution .

This research work includes three parts, with the first section describing the synthesis and applications of neutral 3-coordinate aluminum complexes. As demonstrated in this part, aluminum complexes in a 3-coordinate geometry can be formed only with a ring size greater than or equal to a 6-member ring when supported by diamido ligands. It is found that 1,2-diamido ligands designed for 5-member ring formations can accommodate the formation of only 4-coordinate dinuclear species, which show no activity when used as a single component catalyst in the ring-opening polymerization (ROP) of cyclic esters under specified reaction conditions. Three-coordinate neutral (1,4-diamido)AlMe complexes are successfully synthesized, revealing a higher activity in the ROP of cyclic esters than the existing 6-member analogues under the same reaction conditions. A detailed discussion of the structure-reactivity relationship of Al catalysts in the ROP of cyclic esters is presented. The second part of this thesis project consists of investigations into the applications of 1,4-diamido ligands for the formation of 3-coordinate NHP (N-heterocyclic phosphine) and 2-coordinate NHP+ cations (phosphenium cations). These novel NHP species are the first to be shown in a 7-member ring supported by 1,4-diamido ligands. Various N-substituents in the 1,4-diamido ligands are examined for the formation of a cyclic structure based on their steric hindrance. It is found that a Dipp (2,6-diisopropylphenyl) group is unable to allow for the formation of a 7-member NHP due to its excessive steric bulk. The less bulky mesityl (2,4,6-trimethylphenyl) group at the N-positions in the ligands leads to successful formation of these novel NHPs and NHP+ species. Furthermore, an investigation is carried out to explore their π-accepting property by means of 31P NMR studies. The NHP and NHP+ species synthesized in this project show chemical shifts downfield relative to the existing 5- and 6-member analogues in 31P NMR experiments, suggesting a high potential of 7-member NHPs to be used as π-acceptor ligands. The second section also examined the resulting NHPs and NHP+ species for coordinating to various metals. The last part of this research work is dedicated to presenting the first example of chelating 3–triNHC (tri-N-heterocyclic carbene) ligands that allow for the formation of (triNHC)Pd(II) complexes in a meridional fashion, wherein the triNHC ligand coordinates to the metal center in a pseudo-meridional fashion. Novel [(triNHC)MePdX]X (X = Cl or acetate) complexes are successfully synthesized, and they display extraordinary stability against air and heat. Low activities of the resulting complexes are found in promoting C-C coupling reactions, possibly due to the low solubility of the resulting complexes in organic solvents. Various attempts to change the N-substituents to groups other than methyls are conducted to improve the solubility of the complexes in organic solvents for higher activities in C-C coupling reactions. The results from these attempted modifications to these complexes are discussed in detail. All complexes are characterized by standard spectral methods such as mass spectrometry, X-ray crystallography, elemental analysis, 1H NMR, 13C NMR and 31P NMR spectroscopy.

Introduction: Based on the perceived risk to newborns and pregnancy outcomes associated with certain drugs, women may be hesitant to prescribe and take drugs during pregnancy. In cases like these, pregnant women may seek treatment using natural health products (NHPs) as alternatives to drugs. Unfortunately, evidence of safety in pregnancy and lactation is unknown for many NHPs. Objectives: To review the present state of evidence on the safety of NHPs during pregnancy and lactation. To create a new system to validate evidence on NHPs during pregnancy and lactation designed to affect medical decision. Methodology: NHPs were systematically reviewed and in some cases, meta-analyzed for evidence of safety during pregnancy and lactation. Results: In total, 79 NHPs were systematically reviewed and 2 NHPs were meta-analyzed in order to determine the evidence of safety in pregnancy and lactation. Despite the presence of data (72/79 NHPs in pregnancy and 53/77 NHPs in lactation), the quality of the data was generally poor. Using evidence-based medicine principles, a new system of evaluating evidence was established for studies involving NHPs in pregnancy and lactation. A number of NHPs were identified as being of potential risk in pregnancy. A number of NHPs were identified as potentially being apparently safe in pregnancy and lactation. Blue cohosh is of potential concern for harm in pregnancy given an apparent dose-dependant relationship. Conclusion: There is a large knowledge gap on the safety of NHPs in pregnancy, even more so in lactation. The new system for evaluating NHP safety in pregnancy and lactation will require validation. In order to improve the knowledge gap, future studies are proposed on NHPs in pregnancy and lactation as part of the newly formed MotherNature research network.

Introduction: Based on the perceived risk to newborns and pregnancy outcomes associated with certain drugs, women may be hesitant to prescribe and take drugs during pregnancy. In cases like these, pregnant women may seek treatment using natural health products (NHPs) as alternatives to drugs. Unfortunately, evidence of safety in pregnancy and lactation is unknown for many NHPs. Objectives: To review the present state of evidence on the safety of NHPs during pregnancy and lactation. To create a new system to validate evidence on NHPs during pregnancy and lactation designed to affect medical decision. Methodology: NHPs were systematically reviewed and in some cases, meta-analyzed for evidence of safety during pregnancy and lactation. Results: In total, 79 NHPs were systematically reviewed and 2 NHPs were meta-analyzed in order to determine the evidence of safety in pregnancy and lactation. Despite the presence of data (72/79 NHPs in pregnancy and 53/77 NHPs in lactation), the quality of the data was generally poor. Using evidence-based medicine principles, a new system of evaluating evidence was established for studies involving NHPs in pregnancy and lactation. A number of NHPs were identified as being of potential risk in pregnancy. A number of NHPs were identified as potentially being apparently safe in pregnancy and lactation. Blue cohosh is of potential concern for harm in pregnancy given an apparent dose-dependant relationship. Conclusion: There is a large knowledge gap on the safety of NHPs in pregnancy, even more so in lactation. The new system for evaluating NHP safety in pregnancy and lactation will require validation. In order to improve the knowledge gap, future studies are proposed on NHPs in pregnancy and lactation as part of the newly formed MotherNature research network.

For humans and non-human primates (NHPs) the face represents a particularly important source of social information providing a means of conspecific recognition and cues to personal details including sex, age, and emotional state. The human face may also be fundamental in the transmission to conspecifics of other forms of socially relevant information including the display of facial traits associated with sexual attraction and mate choice. A wealth of experimental literature indicates that humans display robust preferences for certain facial traits associated with facial attractiveness including preferences for bilateral facial symmetry, facial averageness and sexually dimorphic faces and facial features. It is thought that these preferences have evolved via sexual selection, and may be adaptive, due to the role that these specific facial features play in reliably signalling to others the possession of heritable genetic quality or ‘good genes’. Therefore, from an evolutionary perspective, it is possible that certain facial preferences may represent an evolutionary adaptation for the selection of potential mate quality. However, despite similarities between human and NHP face processing and recognition abilities, the shared evolutionary history and social importance of faces to primates in general, and the potential importance of these preferences in the mate choice decisions of NHPs, very little research has investigated the extent to which NHPs display comparable preferences to humans for these specific facial traits. Consequently, the aim of the following thesis was to comparatively assess the general and more specific preferences that humans and NHPs display for faces and for traits associated with facial attractiveness. Data was compiled from preference studies examining the visual preferences displayed by two species of NHP (brown capuchins (Cebus apella) and chimpanzees (Pan troglodytes)) for conspecific faces manipulated for those facial traits associated with attractiveness, and from a single study of brown capuchins examining their general visual preferences for various types of facial information. Comparative preference studies were also conducted upon human adults and infants examining the visual and declared preferences that they display for manipulations of facial attractiveness. Data showed that despite possessing general preferences for certain faces and facial information, generally NHPs displayed no significant preferences for those facial traits thought to influences judgements of attractiveness in humans. Possible reasons for this absence of preference for these particular facial traits and the evolutionary implications of these findings are discussed.

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Natural health products (NHPs) are attractive due to the public’s perception that they are natural and safe but there is wide variety of risks associated with these products. Post-market surveillance is the key to control hazards produced from NHPs. A set of activities are involved in post-market surveillance designed to assure the safety, efficacy and quality of products after being launched into the market. Although post-market surveillance is an efficient tool to preserve the safety of users from adverse reactions of NHPs but there are various challenges associated with performing post-market surveillance specifically for NHPs. This research project is focused on defining a framework for performing post-market surveillance for NHPs and on identifying best practices in its application. An international comparative analysis was undertaken to formulate best practices by reviewing existing frameworks for post-market surveillance of NHPs in Australia, Germany, New Zealand, United Kingdom and United States. Evidence-based best practices are compared with the Canadian post-market surveillance framework to identify key gaps in the Canadian system. Recommendations are provided for bridging each gap, and making the Canadian NHPs surveillance system, strong according to the international standards of best practices.